caa a22 4500 44579755X CHVBK 20180317145130.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s10620-010-1312-4 doi (NATIONALLICENCE)springer-10.1007/s10620-010-1312-4 DNA Methylation in the Rectal Mucosa Is Associated with Crypt Proliferation and Fecal Short-Chain Fatty Acids [Elektronische Daten] [Daniel Worthley, Vicki Whitehall, Richard Le Leu, Natsumi Irahara, Ronald Buttenshaw, Kylie-Ann Mallitt, Sonia Greco, Ingunn Ramsnes, Jean Winter, Ying Hu, Shuji Ogino, Graeme Young, Barbara Leggett] Background: DNA methylation varies throughout the normal colorectal mucosa and DNA methylation in normal appearing mucosa is associated with serrated and adenomatous neoplasia elsewhere within the colorectum. Aims: The purpose of this study was to measure luminal chemistry, rectal proliferation and mucosal DNA methylation and thus determine whether regional and pathological patterns of DNA methylation could be explained by luminal and epithelial factors. Methods: Twenty healthy subjects had normal rectal mucosal biopsies and a 24-h fecal collection. Rectal biopsies were analyzed for epithelial proliferation (Ki67 immunohistochemistry) and DNA methylation at 17 different markers, including "type A” markers (ESR1, GATA5, HIC1, HPP1, SFRP1), "type C” markers (MGMT, MLH1, CDKN2A, MINT1, MINT2, MINT31, IGF2, CACNA1G, NEUROG1, SOCS1, RUNX3), and LINE-1. Fecal analysis included short-chain fatty acids (SCFA), pH and ammonia. Mean "type A” and CIMP panel methylation Z-scores were calculated. Results: Rectal proliferation was significantly correlated with methylation at ESR1 (ρ=0.81, P=0.003) and GATA5 (ρ=0.78, P=0.012). LINE-1 methylation was 71.7 vs. 74.1%, in patients with "low” and "high” fecal total SCFA concentration (defined by the median value), respectively (P=0.0019). On multivariate linear regression "type A” methylation was independently associated with rectal proliferation (P=0.001). LINE-1 methylation was directly associated with rectal proliferation (P=0.038) and total fecal SCFA concentration (P=0.002), and inversely associated with fecal NH3 concentrations (P=0.003). Conclusions: DNA methylation in normal rectal mucosa is associated with crypt proliferation and fecal SCFA concentration. These associations may help to explain regional differences in DNA methylation as well as providing a possible link between the colorectal lumen and carcinogenesis. Springer Science+Business Media, LLC, 2010 DNA methylation nationallicence Epigenetics nationallicence Colorectal cancer nationallicence Carcinogenesis nationallicence CIMP : CpG island methylator phenotype nationallicence CIN : Chromosomal instability nationallicence CRC : Colorectal cancer nationallicence PMR : Percent of methylated reference nationallicence Worthley Daniel Conjoint Gastroenterology Laboratory, Royal Brisbane and Women's Hospital Research Foundation Clinical Research Centre, Brisbane, QLD, Australia aut Whitehall Vicki Conjoint Gastroenterology Laboratory, Royal Brisbane and Women's Hospital Research Foundation Clinical Research Centre, Brisbane, QLD, Australia aut Le Leu Richard Flinders Centre for Cancer Prevention and Control, Flinders University of South Australia, Adelaide, SA, Australia aut Irahara Natsumi Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA aut Buttenshaw Ronald Conjoint Gastroenterology Laboratory, Royal Brisbane and Women's Hospital Research Foundation Clinical Research Centre, Brisbane, QLD, Australia aut Mallitt Kylie-Ann Statistics Unit, Queensland Institute of Medical Research, Brisbane, QLD, Australia aut Greco Sonia Conjoint Gastroenterology Laboratory, Royal Brisbane and Women's Hospital Research Foundation Clinical Research Centre, Brisbane, QLD, Australia aut Ramsnes Ingunn Conjoint Gastroenterology Laboratory, Royal Brisbane and Women's Hospital Research Foundation Clinical Research Centre, Brisbane, QLD, Australia aut Winter Jean Flinders Centre for Cancer Prevention and Control, Flinders University of South Australia, Adelaide, SA, Australia aut Hu Ying Flinders Centre for Cancer Prevention and Control, Flinders University of South Australia, Adelaide, SA, Australia aut Ogino Shuji Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA aut Young Graeme Flinders Centre for Cancer Prevention and Control, Flinders University of South Australia, Adelaide, SA, Australia aut Leggett Barbara Conjoint Gastroenterology Laboratory, Royal Brisbane and Women's Hospital Research Foundation Clinical Research Centre, Brisbane, QLD, Australia aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/2(2011-02-01), 387-396 0163-2116 56:2<387 2011 56 10620 https://doi.org/10.1007/s10620-010-1312-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-010-1312-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Worthley Daniel Conjoint Gastroenterology Laboratory, Royal Brisbane and Women's Hospital Research Foundation Clinical Research Centre, Brisbane, QLD, Australia aut NATIONALLICENCE 700 1- Whitehall Vicki Conjoint Gastroenterology Laboratory, Royal Brisbane and Women's Hospital Research Foundation Clinical Research Centre, Brisbane, QLD, Australia aut NATIONALLICENCE 700 1- Le Leu Richard Flinders Centre for Cancer Prevention and Control, Flinders University of South Australia, Adelaide, SA, Australia aut NATIONALLICENCE 700 1- Irahara Natsumi Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA aut NATIONALLICENCE 700 1- Buttenshaw Ronald Conjoint Gastroenterology Laboratory, Royal Brisbane and Women's Hospital Research Foundation Clinical Research Centre, Brisbane, QLD, Australia aut NATIONALLICENCE 700 1- Mallitt Kylie-Ann Statistics Unit, Queensland Institute of Medical Research, Brisbane, QLD, Australia aut NATIONALLICENCE 700 1- Greco Sonia Conjoint Gastroenterology Laboratory, Royal Brisbane and Women's Hospital Research Foundation Clinical Research Centre, Brisbane, QLD, Australia aut NATIONALLICENCE 700 1- Ramsnes Ingunn Conjoint Gastroenterology Laboratory, Royal Brisbane and Women's Hospital Research Foundation Clinical Research Centre, Brisbane, QLD, Australia aut NATIONALLICENCE 700 1- Winter Jean Flinders Centre for Cancer Prevention and Control, Flinders University of South Australia, Adelaide, SA, Australia aut NATIONALLICENCE 700 1- Hu Ying Flinders Centre for Cancer Prevention and Control, Flinders University of South Australia, Adelaide, SA, Australia aut NATIONALLICENCE 700 1- Ogino Shuji Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA aut NATIONALLICENCE 700 1- Young Graeme Flinders Centre for Cancer Prevention and Control, Flinders University of South Australia, Adelaide, SA, Australia aut NATIONALLICENCE 700 1- Leggett Barbara Conjoint Gastroenterology Laboratory, Royal Brisbane and Women's Hospital Research Foundation Clinical Research Centre, Brisbane, QLD, Australia aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/2(2011-02-01), 387-396 0163-2116 56:2<387 2011 56 10620 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer